Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When viewed from the perspective of time, human genetic disorders give new insights into their etiology and evolution. Here, we have correlated a specific set of Alu repetitive DNA elements, known to be the basis of certain genetic defects, with their phylogenetic roots in primate evolution. From a differential distribution of Alu repeats among primate species, we identify the phylogenetic roots of three human genetic diseases involving the LPL, ApoB, and HPRT genes. The different phylogenetic age of these genetic disorders could explain the different susceptibility of various primate species to genetic diseases. Our results show that LPL deficiency is the oldest and should affect humans, apes, and monkeys. ApoB deficiency should affect humans and great apes, while a disorder in the HPRT gene (leading to the Lesch-Nyhan syndrome) is unique to human, chimpanzee, and gorilla. Similar results can be obtained for cancer. We submit that de novo transpositions of Alu elements, and saltatory appearances of Alu-mediated genetic disorders, represent singularities, places where behavior changes suddenly. Alus' propensity to spread, not only increased the regulatory and developmental complexity of the primate genome, it also increased its instability and susceptibility to genetic defects and cancer. The dynamic spread not only provided markers of primate phylogeny, it must have actively shaped the course of that phylogeny.
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PMID:Human genetic disorders, a phylogenetic perspective. 1135 Jan 62